Therapy Resistance in Melanoma Drives Ciliogenesis and Glutamine/aspartate Metabolism Dependency
Year: 2026
Type: preprint
Abstract: ABSTRACT Despite the remarkable success of new therapeutic approaches, a considerable number of melanoma patients still relapse on conventional therapies within two years and develop resistance. Alterations in metabolism, including amino acid availability and regulation of metabolic processes, have been implicated in acquired drug resistance. In this study, we developed in vitro and in vivo models of target therapy resistance (TTR) and identified a genetic program that supports primary ciliogenesis in drug-resistant BRAF melanoma. We established that drug resistance enhances ciliogenesis, which is needed to respond and survive to combination therapy (CT). Mechanistically, impairing cilia formation (IFT88 KO ) rewires glutamine and aspartate metabolism. Overall, we provide a new molecular mechanism underlying therapy resistance that should be considered to tailored therapeutic strategies.
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221706627